Lung Organoids

The lungs are composed of highly branched tube systems that bring air into the alveoli, where gas exchange takes place. The proximal and distal regions of the lung contain epithelial cells dedicated to different functions: basal, secretory and ciliated cells in the airway, and type I and type II cells lining the alveoli. Damage to these epithelial cells may lead to inflammatory storms and progressive diseases, including bronchial asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), as well as respiratory infections.

Recent advances in isolating lung epithelial progenitor cells and stromal cells, as well as defining stem cell niche factors that are essential for lung development, have led to the establishment of an in vitro three-dimensional (3D) culture system: lung organoids, also known as pulmonary organoids or airway organoids.

Lung organoids are essentially 3D tissue-engineered mini lungs that accurately replicate the histological and functional aspects of the in vivo tissue. By developing these structures and functions, organoids emulate the physiological or pathological environment in the body. They usually have multiple types of cells mirroring their counterpart and native extracellular matrix (ECM) constituents, and are typically miniature or micro-scale in size.

The most attractive advantage of lung organoid culture is that it allows for the expansion of lung stem cell populations and the induction of differentiated cells from a very limited starting material. In addition, it provides a more physiologically relevant culture system, especially for the distal lung. These special features make organoid culture an excellent culture system widely used in both basic and translational methods such as drug screening, disease modeling and genetic screening.

At OrganoLab, we combined adult human primary bronchial epithelial cells, lung microvascular endothelial cells and lung fibroblasts in 3D culture conditions to generate lung organoids. By combining epithelial differentiation conditions with a multicellular aggregation culture system, we have generated self-assembling lung organoids that are amenable to study cell-cell interactions. This system represents a novel tool for studying disease-relevant cellular and molecular function.

References

1. Li Y, et al.; Organoids as a Powerful Model for Respiratory Diseases. Stem Cells International, 2020, 1-8.
2. Miller, A. J. et al.; (2019). Generation of lung organoids from human pluripotent stem cells in vitro. Nature Protocols, 2019, 14: 518-540.
3. Barkauskas, Christina E. et al.; Lung organoids: current uses and future promise. Development, 2017, 144(6): 986-997.
4. Tan Q, et al.; Human airway organoid engineering as a step toward lung regeneration and disease modeling. Biomaterials, 2017, 113: 118-132.
5. Nikolić, M. Z. et al.; Lung Organoids and Their Use to Study Cell-Cell Interaction. Current Pathobiology Reports, 2017, 5(2): 223-231.